Advanced age is associated with an increased risk of infection. Abnormalities of neutrophil (PMN) function may predispose to infection in the elderly. PMN adhesion, an early response in inflammation, plays an important role in the localization of infection and prevention of the dissemination of microorganisms in the host. Altered PMN adhesive response to inflammatory stimuli may underly the increased risk and poor containment of infections in the elderly. Mechanisms involved in activated PMN adhesiveness are not well characterized. Prior work in our laboratory has indicated that the macroglycoprotein, fibronectin (Fn), plays a role in stimulated PMN adherence. In further studies we demonstrated that defective PMN adherence after thermal injury in humans is associated with abnormalities of PMN Fn physiology. The aims of this proposal are, first, to characterize PMN adhesiveness (adherence and aggregation) in the elderly with acute infections compared with a younger population with similar infections. The second aim involves examining Fn physiology and its relationship to PMN adhesiveness in the elderly. This will include a qualitative and quantitative examination of plasma Fn, subcellular localization of Fn on PMN, and the release and binding of Fn to PMN. The approach to the first aim will involve determining the stimulus specificity and reversibility of PMN adherence and aggregation during episodes of acute infection in the elderly. The duration of PMN dysfunction will be assessed by re-examining PMN from patients following resolution of infection. An understanding of the effect of purified Fn, Fn-rich cryoprecipitate, or plasma on PMN adhesiveness will aid in the isolation of inhibitory or adhesive factors in the plasma. The approach to the second aim will involve quantitation of plasma Fn levels in various age groups during periods of acute infection by radioimmunoassay (RIA). Qualitative differences in plasma Fn between older and younger adult subjects with infections will be addressed by immunoprecipitation of plasma with antibody to human Fn. Altered subcellular localization of Fn within PMN may be vital in the pathophysiology of abnormal PMN adhesion. Subcellular fractions of PMN will be isolated by nitrogen cavitation and differential centrifugation and immunoreactive Fn in fractions quantitated by RIA. Quantitation of immunoreactive Fn in supernatants of stimulated and unstimulated PMN will identify abnormalitites in release of Fn from PMN of elderly subjects. The question of altered Fn receptor physiology in PMN will be addressed by quantifying the binding of radiolabeled Fn to adherent or nonadherent PMN in the presence or absence of stimulus. Potential reversal of altered PMN adhesiveness will be examined in the presence of purified Fn, cryoprecipitate or plasma. The data gathered from this proposal may add significantly to our knowledge of in vitro alterations of PMN adhesive dysfunction and susceptibility to infection in the elderly. A definition of PMN adhesiveness would permit certain predictions concerning responsiveness to infections and means of regulating altered PMN adhesion.